Improved fidelity of brain microstructure mapping from single-shell diffusion MRI

Diffusion weighted imaging (DWI) is sensitive to alterations in the diffusion of water molecules caused by microstructural barriers. Different microstructural compartments are characterized by differences in DWI signal. Diffusion tensor imaging conflates the signal from these compartments into a single tensor, which poorly represents multiple white matter fascicles and extra-axonal space. Diffusion compartment imaging (DCI) models overcome this limitation by providing parametric representations for the signal contribution of each compartment, thereby improving the fidelity of brain microstructure mapping. However, current approaches fail to identify DCI model parameters from conventional single-shell DWI with the desired accuracy. It has been demonstrated that part of this inaccuracy is due to the ill-posedness of the estimation of DCI model parameters from conventional single-shell acquisitions. In this paper, we propose to regularize the estimation problem for single-shell DWI by learning a prior distribution of DCI model parameters from DWI acquired at multiple b-values in an external population of subjects. We demonstrate that this population-informed prior enables, for the first time, accurate estimation of DCI models from single-shell DWI typically acquired in clinical practice. We validated our approach on synthetic and in vivo data of healthy subjects and patients with autism spectrum disorder. We applied the approach to population studies of brain microstructure in autism and found that introducing a population-informed prior leads to reliable detection of group differences. Our algorithm enables novel investigation from large existing DWI datasets in normal development and in disease and injury.